Association between drugs and vaccines commonly prescribed to older people and bullous pemphigoid: a case-control...

Bullous pemphigoid (BP) is an autoimmune skin disease that mainly affects older people. Based on case series and small hospital-based studies, a number of drugs have been associated with BP. More reliable and precise estimates of associations between a broad selection of drugs/vaccines and BP will enable greater awareness of any potential increased risk of BP following the administration of certain medicines and help identify clinical, histological and genomic characteristics of drug-induced BP for different culprit drugs. Greater awareness could lead to earlier recognition or suspicion of BP and referral to a dermatologist for diagnosis. Earlier diagnosis may lead to less aggressive treatment and improved wellbeing.

To determine the association between drugs/vaccines commonly prescribed to older people and the risk of developing BP.

We conducted a population-based nested case-control study between 1998 and 2021 using electronic primary care records from the Clinical Practice Research Datalink. We matched patients with BP with up to five controls. Exposures were drugs/vaccines commonly prescribed to older people. We used multivariable conditional logistic regression adjusting for multiple drug use. For antibiotics, in a sensitivity analysis, we considered that drugs may be prescribed for undiagnosed symptoms of BP that resemble skin infection (protopathic bias).

Antibiotics were associated with the highest risk of BP [odds ratio (OR) 4.60, 95% confidence interval (CI) 4.40-4.80]. However, after adjusting for protopathic bias, the OR decreased to 2.08 (95% CI 1.99-2.17). Also, after adjusting for protopathic bias, of all the antibiotic classes and subclasses, penicillins [OR 3.44, 95% CI 3.29-3.60 (sensitivity analysis OR 1.74, 95% CI 1.66-1.84)] and penicillinase-resistant penicillins [OR 7.56, 95% CI 7.15-8.00 (sensitivity analysis OR 2.64, 95% CI 2.45-2.85)] had the strongest associations with BP risk. Other drugs strongly associated with increased risk were gliptins (OR 2.77, 95% CI 2.37-3.23) and second-generation antipsychotics (OR 2.58, 95% CI 2.20-3.03).

Healthcare professionals need to be aware of BP risk in older people, particularly when prescribing penicillinase-resistant penicillins, gliptins and second-generation antipsychotic drugs, to recognize and manage BP early. Owing to the low disease prevalence, we do not suggest avoiding certain drugs/vaccines to prevent BP. Further research should consider recency, dosage and duration of antibiotic treatments.